Functional correlates of cognitive dysfunction in multiple sclerosis: A multicenter fMRI Study

Abstract

In this multicenter study, we applied functional magnetic resonance imaging (fMRI) to define the functional correlates of cognitive dysfunction in patients with multiple sclerosis (MS). fMRI scans during the performance of the N-back task were acquired from 42 right-handed relapsing remitting (RR) MS patients and 52 sex-matched right-handed healthy controls, studied at six European sites using 3.0 Tesla scanners. Patients with at least two abnormal (<2 standard deviations from the normative values) neuropsychological tests at a standardized evaluation were considered cognitively impaired (CI). FMRI data were analyzed using the SPM8 software, modeling regions showing load-dependent activations/deactivations with increasing task difficulty. Twenty (47%) MS patients were CI. During the N-back load condition, compared to controls and CI patients, cognitively preserved (CP) patients had increased recruitment of the right dorsolateral prefrontal cortex. As a function of increasing task difficulty, CI MS patients had reduced activations of several areas located in the fronto-parieto-temporal lobes as well as reduced deactivations of regions which are part of the default mode network compared to the other two groups. Significant correlations were found between abnormal fMRI patterns of activations and deactivations and behavioral measures, cognitive performance, and brain T2 and T1 lesion volumes. This multicenter study supports the theory that a preserved fMRI activity of the frontal lobe is associated with a better cognitive profile in MS patients. It also indicates the feasibility of fMRI to monitor disease evolution and treatment effects in future studies.

Fatigue and cognition: Pupillary responses to problem‐solving in early multiple sclerosis patients

“…This indicates that for most of the patients task‐related allocation of attention is well‐functioning, facilitating efficient cognitive processing. This is in accordance with the recent fMRI results of cognitive processing of early MS patients, where normal activation patterns were found in the cognitively preserved patients (Rocca, Valsasina, et al., ).…”

“…In this study, we investigated the pupillary response to problem- where normal activation patterns were found in the cognitively preserved patients (Rocca, Valsasina, et al, 2014).…”

Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis

“…Our findings are consistent with results from a recent multicenter trial by Rocca et al ., where 42 RRMS patients were evaluated during the N-back load condition, showing that the 22 cognitively preserved patients had increased recruitment of the right dorsolateral prefrontal cortex during the cognitive task. 35 In this study, the greater BOLD activation seen in MSNI, also correlated with I/DMT performance (based on A′ scores), with T2LV and with EDSS, supporting the notion the higher lesion load not only correlates with higher disability but may interfere with connections/input from different brain regions involved in cognition. As T2LV increases, there seems to be a decrease in the brain's ability to compensate (by either increasing activation or activating additional regions) for the disruption of input to areas involved in performing a cognitive task…”

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis

“…BRB‐N includes the Selective Reminding Test (SRT), to assess verbal memory; the 10/36 Spatial Recall Test (10/36 SRT), to assess visual memory; the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) 2” and 3”, to assess attention and information processing speed; and the Word List Generation (WLG) test, to assess verbal fluency. As previously described [Rocca et al, ; Sepulcre et al, ], raw data were corrected according to normative values and Z ‐scores for each of the previous domains were calculated.…”